Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease

  • Review
  • Intervention




The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease were conflicting and controversial. A meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease.


To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease.

Search strategy

Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched.

Selection criteria

Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms.

Data collection and analysis

Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView).

Main results

The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment > 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3.88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14.

Authors' conclusions

Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after > 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.

Plain language summary

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease

Azathioprine and 6-mercaptopurine may be effective for inducing remission in Crohn's disease among patients with chronically active disease. These drugs may reduce the need for steroid treatment and their use may therefore lead to a lower incidence of steroid related side effects. However, these drugs are slow acting and are associated with some rare, but serious side effects. In some patients they suppress formation of blood cells that fight off infection and allow blood to clot and they occasionally cause inflammation of the pancreas. For these reasons careful consideration needs to be given to the use of these drugs as the primary treatment for patients experiencing an acute flare of Crohn's disease.